Universität zu Köln

Sigaroudi, Ali ORCID: 0000-0002-3176-4631, Kinzig, Martina, Wahl, Oliver, Stelzer, Christoph, Schroeter, Michael, Fuhr, Uwe, Holzgrabe, Ulrike and Soergel, Fritz (2018). Quantification of Hydrochlorothiazide and Ramipril/Ramiprilate in Blood Serum and Cerebrospinal Fluid: A Pharmacokinetic Assessment of Central Nervous System Adverse Effects. Pharmacology, 102 (3-4). S. 133 - 138. BASEL: KARGER. ISSN 1423-0313

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Abstract

Background: A drug must reach the central nervous system (CNS) in order to directly cause CNS adverse effects (AEs). Our current study addressed the pharmacokinetic (PK) background of the assumption that CNS concentrations of hydrochlorothiazide (HCT) and ramiprilate may directly cause CNS AEs such as headache and drowsiness. Methods: In neurological patients, paired serum and cerebrospinal fluid (CSF) samples were withdrawn simultaneously. Some of them were treated with HCT (n = 15, daily chronic doses 7.5-25 mg) or ramipril (n = 9, 2.5-10 mg). Total concentrations of HCT and ramiprilate were quantified in these samples. To this end, sensitive liquid chromatography/tandem mass spectrometry methods were developed. Results: CSF reached 4.1% (interquartile ranges 2.5-5%) of total serum concentrations for HCT and 2.3% (1.7-5.7%) for ramiprilate, corresponding to about 11.3% and 5.5% of respective unbound serum concentrations. Conclusion: The PK/Pharmacodynamic characteristics of HCT and ramiprilate in the CNS are unknown. However, since the CSF levels of these agents, both free and bound, were much lower than the corresponding concentrations in serum, it is unlikely that the observed CNS AEs are mediated primarily via direct effects in the brain. (C) 2018 S. Karger AG, Basel

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Sigaroudi, Ali UNSPECIFIED orcid.org/0000-0002-3176-4631 UNSPECIFIED Kinzig, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Wahl, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED Stelzer, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeter, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Fuhr, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Holzgrabe, Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Soergel, Fritz UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-201982
DOI:	10.1159/000489999
Journal or Publication Title:	Pharmacology
Volume:	102
Number:	3-4
Page Range:	S. 133 - 138
Date:	2018
Publisher:	KARGER
Place of Publication:	BASEL
ISSN:	1423-0313
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ANGIOTENSIN-CONVERTING ENZYME; ACETAZOLAMIDE; COTRANSPORT Multiple languages Pharmacology & Pharmacy Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/20198